Recent developments in ligands and chemical probes targeting solute carrier transporters

Curr Opin Chem Biol. 2021 Jun;62:53-63. doi: 10.1016/j.cbpa.2021.01.012. Epub 2021 Mar 6.


Solute carrier (SLC) membrane transporters remain a largely unexploited target class, despite their central roles in cell identity and metabolism. This gap is reflected in the lack of high-quality chemical ligands or probes and in the small number of compounds that have progressed toward clinical development. In this review, we discuss recent advancements in SLC ligand discovery as well as new candidates that have been added to the investigational toolkit, with a particular focus on first-in-class ligands and the cognate discovery strategies. The availability of new probes expands the opportunity to elucidate the functions of SLCs and their relevance in physiology and explores any future potential of SLC druggability.

Keywords: Cancer; Drug discovery; First-in-class ligands; Ligand discovery; Modulators of neurotransmission; PET tracers; Small-molecule probes; Solute carrier (SLC) transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Biological Transport / drug effects*
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Drug Discovery
  • Humans
  • Ligands
  • Metabolic Diseases
  • Neoplasms / drug therapy
  • Neurotransmitter Agents / metabolism
  • Nutrients / metabolism
  • Protein Binding
  • Protein Conformation
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Solute Carrier Proteins / metabolism*


  • Antineoplastic Agents
  • Ligands
  • Neurotransmitter Agents
  • Small Molecule Libraries
  • Solute Carrier Proteins